Clinical predictors of pathological response after immunotherapy in salvage surgery for non-small cell lung cancer: a supplementary analysis of the CReGYT-05 immune checkpoint inhibitor-salvage study.

OBJECTIVES: Radiological responses based on tumor size reduction are often unreliable after immune checkpoint inhibitor (ICI) therapy for non-small cell lung cancer (NSCLC), particularly in salvage surgery. The aim of this study was to evaluate the association between MPR and prognosis, and to determine whether changes in metabolic response on positron emission tomography/computed tomography (PET/CT) and tumor marker levels can identify patients who achieve a major pathological response (MPR) despite residual disease.

METHODS: This multicenter retrospective study (CReGYT-05 ICI-Salvage study) included patients with NSCLC who underwent salvage lung resection after ICI therapy at 14 institutions in Japan. Metabolic response was evaluated by changes in maximum standardized uptake value (SUVmax). Pathological response was classified as MPR (≦10% viable tumor cells). Associations among metabolic response, tumor markers, pathological response, and survival were analyzed.

RESULTS: Among 31 evaluable patients, 11 (35%) achieved MPR. Patients with MPR had improved 5-year overall survival compared with those without MPR (100% vs. 40.3%; p = 0.017). In univariate analysis, serum CEA decreased (odds ratio [OR], 16.000; 95% confidence interval [CI], 2.105-343.167; p = 0.005), SUVmax decreased ≧60% (OR, 25.000; 95% CI, 2.441-661.493; p = 0.005), and cStage IV (OR, 0.125; 95% CI, 0.020-0.608; p = 0.009) were suggested to be associated with MPR.

CONCLUSIONS: Radiologic response alone is insufficient to identify major pathological responders after ICI therapy. PET/CT metabolic response combined with tumor marker changes provides clinically meaningful information for selecting candidates for salvage surgery.